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Rett syndrome

This is part of Rare diseases.

Diagnosis: Rett syndrome

Synonyms: --

Innehåll


Date of publication: 2014-10-08
Version: 4.0

ICD 10 code

F84.2

The disease

Rett syndrome is a neurodevelopmental disorder caused by abnormalities in the way the brain matures, and leads to severe disabilities. The syndrome occurs primarily in girls and women and usually presents at between 6 and 18 months of age. Until then, the child's development appears to be normal.

The syndrome is named after the Viennese paediatrician Andreas Rett, who in 1965 published a study of girls and women with identical symptoms and patterns of disease progression. Although the first girls in Sweden with the syndrome had been observed some years previously by Professor Bengt Hagberg, Rett syndrome did not become internationally recognized until 1983 when a study was published of 35 girls from Gothenburg, Paris and Lisbon.

Occurrence

Rett syndrome occurs all over the world. Every year in Sweden an average of five or six girls are born who subsequently develop the syndrome. The prevalence of the disease in Sweden is estimated at 10 per 100,000 girls and women. In total, approximately 300 females have been diagnosed with Rett syndrome in Sweden.

The syndrome also occurs in a few boys and men.

Cause

Rett syndrome is defined on the basis of symptoms and the characteristic course of the disease. Over 90 per cent of the girls and women with the most common variety of Rett syndrome can be shown to have a mutation in a gene located furthest out on the long arm of the X chromosome (Xq28). This gene, MECP2, controls the formation of (codes for) a protein, MECP2, the full name of which is methyl CpG binding protein 2. The role of this protein is to regulate some other genes which are important for the development and normal function of nerve cells. Gene MECP2 can both activate and de-activate a number of other genes.

As a result of the mutation the protein does not stabilize normally, which in turn affects the maturity of the nerve cells. Filaments in the nerve cells (axons and dendrites) do not grow and branch normally, the connections between nerve cells (synapses) become fewer, and the nerve cells become more tightly packed than normal. As the nerve cells in the brain stem are affected at an early stage the maturity of the whole brain is affected, which in turn affects control of the autonomic nervous system (that part of the nervous system not subject to voluntary control). This causes symptoms which to varying degrees affect control of respiration, pulse, blood pressure and peripheral circulation.

Symptoms similar to those of Rett syndrome, in combination with neonatal seizures, may also be caused by mutations in genes CDKL5 and FOXG1.

Heredity

The mutated MECP2 gene is situated on the X chromosome, which is one of the chromosomes determining sex. Men have one X chromosome and one Y chromosome, while women have two X chromosomes. Rett syndrome occurs primarily in females as males with the mutation on their sole X chromosome are often so severely affected that they do not survive the foetal stage. (See "Diagnosis" for more information on boys with the syndrome.)

With few exceptions, Rett syndrome is caused by a new mutation. This means that the genetic mutation occurs in an individual for the first time and is not inherited from either parent. Consequently, parents with a child with a new mutation generally have only a slight risk of having another child with the disorder. The risk of having more children with the syndrome is very small (less than 1 per cent).

It is extremely rare, although it has occurred, that a girl with the syndrome has inherited the mutation from her mother. In such cases, the inheritance pattern is X-linked dominant.

Figure: X-linked dominant inheritance via a female carrier with the disease

Symptoms

The symptoms of different individuals with the syndrome vary in severity and according to age. In boys with the syndrome, symptoms often present earlier than in girls and are considerably more difficult to interpret.

Children with Rett syndrome often develop normally until between 6 and 18 months of age. It is characteristic of the syndrome that its progression follows a set pattern over time, during which different symptoms become more or less pronounced. The fully-developed syndrome is associated with severe disability, affecting cognitive abilities, motor skills and communication. Affected children also have epilepsy and other, sudden, non-epileptic seizures, major problems with voluntary movement (dyspraxia), and a lack of coordination of and control over breathing, blood pressure and pulse. People with Rett syndrome often live to middle-age and sometimes into their 60s and beyond.

The syndrome can be divided into four stages.

  • Stage 1 (stagnation) Early, almost imperceptible indications of the syndrome present between the ages of 6 to 18 months, when general development slows down. Muscle tone is often somewhat reduced. In most children the head grows slowly, after having grown normally during the first months of life. This first phase of the disease usually lasts for a few months, but may sometimes be more rapid.
  • Stage II (regression) At some point between the ages of one and four, symptoms become more severe. Children lose skills they have developed, such as the ability to perform purposeful hand movements or use words or sounds they have learned. They cease to play and prattle and it becomes more difficult to make contact with them while they begin to react strongly to changes in physical position and new environments. Repetitive tongue and hand movements characteristic of Rett syndrome (stereotypical movements) begin, as does pronounced tooth grinding (bruxism). During this stage, which may last for weeks or months, children with Rett syndrome will have periods when they appear panic-stricken and cry inconsolably. They may find it very difficult to calm down and normal sleeping patterns are often disrupted.
  • Stage III (plateau) This stage is characterized by increased interest in surroundings, a return of motivation and improved communication. They try to regain lost skills and use their remaining capacities, and they may say a few words and make purposeful hand movements. They may also stand and learn to walk, but their balance is usually impaired. Muscular tone increases and many individuals develop severe curvature of the spine (scoliosis). Communicative abilities may improve and characteristic, intensive eye contact becomes more pronounced. For many with Rett syndrome, the plateau stage of the disease may last for decades or be life-long. Girls usually reach puberty at the expected time.
  • Stage IV (inability to stand/walk without support) This is the stage when people with Rett syndrome cannot stand and become immobile without support. Some individuals never learn to stand or walk, while others who have learned lose these abilities. However, many individuals never reach this stage, but continue to walk all their lives.

The autonomic nervous system

Certain physical functions including the regulation of blood circulation and respiration are governed by the autonomic nervous system with the help of a feedback system which is controlled by the brain stem. In Rett syndrome the immaturity of the brainstem causes a lack of control and coordination of the autonomic nervous system.

Abnormal breathing patterns associated with the syndrome affect the exchange of gases which normally takes place via the lungs and cardiovascular system. They can be divided into three categories, namely forceful breathing, feeble breathing (shallow) and apneustic breathing (a series of slow deep inhalations and a tendency to hold the breath).

Valsalva breathing (attempting to forcibly exhale while the epiglottis is closed) is a common complication in the breathing abnormalities characteristic of Rett syndrome, and affects both the autonomic nerve system and brain stem functions. Valsalva breathing causes a large volume of air, under pressure, to be forced down the gastrointestinal canal, causing it to swell up.

The motility of the gastrointestinal tract (peristalsis) shifts the food along the tract. Movements are controlled and coordinated by the autonomic nervous system. It is common that these movements are impaired, leading to a number of symptoms including severe constipation and stomach pain. Painful inflammation in the lower oesophagus (oesophagitis) can occur from an early age and if the cardia (the part of the stomach attached to the oesophagus) does not close tightly, the child can experience severe bouts of vomiting from an early age.

Instability of pulse and blood pressure may trigger sensations of dizziness, growing anxiety and panic. An imbalance in the autonomic nervous system is also the reason why many people with Rett syndrome have cold, bluish, clammy feet.

Nutrition

Breathing abnormalities, muscular contractions and involuntary movements mean that many people with Rett syndrome expend large amounts of energy. It can be difficult for children to consume sufficient calories, especially during pre-school and early school years, when they are growing. It can also be difficult to co-ordinate breathing and swallowing; periods of breath holding, abnormally shallow breathing and forceful breathing can sometimes make it difficult for those with Rett syndrome to eat or swallow.

Children and adults with the condition often have problems in coordinating movements of the mouth and throat. Eating is a slow process and therefore meals take longer.

Growth

After normal growth during the first months of life, the child's rate of growth decreases and the expected growth spurt at around the age of six is less pronounced than normal. Most adults with the syndrome have a growth deficiency and small hands and feet. This is not associated with abnormal levels of growth hormone.

Abnormalities

Abnormalities in muscular tension (dystonia) may be different on the right and left sides of the body and thus cause malpositioning of the joints of the back, hips, ankles and toes. Spinal deformities (scoliosis) and hunched backs in the upper area of the spine (kyphosis) are common. Deterioration can be very rapid. This is the case during growth spurts, particularly during puberty. Often a gradual deterioration continues in adulthood as skeletal malpositioning does not stabilize when the child stops growing. Neuromuscular scoliosis and kyphosis make it difficult to balance and hold up the head, which interferes with eye contact with others and with normal communication.

Broken bones are often found in those with Rett syndrome. The cause has yet to be established.

Epileptic and non-epileptic seizures

More than three-quarters of people with the condition are affected by some form of seizure. The type varies, and epileptic and non-epileptic seizures can occur separately or together.

Epileptic seizures originate in the cerebral cortex while in Rett syndrome non-epileptic seizures generally originate in the brain stem. In both cases groups of nerve cells are activated, apparently at random, and the resulting symptoms depend on the functions of the nerve cells in this particular area.

In Rett syndrome, attacks originating in the brain stem are called ASBA (Abnormal Spontaneous Brainstem Activation) and affect normal function of nerve cells in this area of the brain. Symptoms include abnormalities in breathing, pulse, blood pressure, eye and eyelid movements, saliva secretion and movements of the tongue, mouth and face. Other symptoms include abnormal head and muscle movements, which can affect levels of consciousness and may be mistaken for epileptic seizures.

These seizures usually start in infancy. Sometimes they present first in the teen years, in which case it is especially important to be aware that they may be ASBA. "Vacant spells" is a term describing periods of mental absence associated with wide-open eyes and abnormal activity in the brain stem. These attacks can be difficult to distinguish from absence seizures - a form of epilepsy.

Epilepsy tends to improve with age, but it should be noted that many seizures judged to be epileptic can originate in the brain stem. A proportion of people with Rett syndrome become virtually free from epileptic seizures in early middle-age or older, without the help of medication.

Insomnia and agitation

Both children and adults with the syndrome often have irregular sleeping patterns and an abnormal daily cycle. Some individuals are awake for periods during the night, when they scream or laugh loudly. Others are anxious or fearful when they wake up and they breathe forcefully before they can relax again. This can be caused by inadequate respiration and should be investigated. Agitation is a common result of irregularities in central autonomic control.

Oral motor function, teeth and abnormal bites

Oral motor function is often impaired, although there are wide individual variations. Both children and adults with the syndrome may have problems moving food to the backs of their mouths, as well as chewing and swallowing, causing an increased risk of choking (aspiration). Grinding of the teeth (bruxism) is common and can lead to tension in jaw muscles. This gives a characteristic grinding sound and causes severe wear on the teeth. Many people with the syndrome make involuntary tongue movements. There may be an overbite or open bite of the front teeth, and the palate may be high and narrow.

Development and communication

People with Rett syndrome lose, completely or partially, voluntary control over their movements at an early age. This is seen most clearly in the hands, but applies to all voluntary movement (dyspraxia). Many individuals have a severe cognitive impairment.

Those with Rett syndrome understand much more, and take in more impressions and experiences, than they can express. Motor problems, an inability to attract attention and difficulty coordinating movements can sometimes mask cognitive and communicative abilities. Many people with the condition are very interested in social contact and communicating, but communication can often take a long time and their response times can be lengthy. Most people with the syndrome cannot speak but often have a distinctive and intense gaze and can make direct eye contact at close quarters. It is important to be aware of this form of contact, and to use it.

Diagnosis

A diagnosis of Rett syndrome is based on the clinical presentation of specific symptoms and a number of characteristic developmental abnormalities.

The discovery of the connection between the syndrome and mutations in gene MECP2 has led to great progress in diagnostics and a better understanding of the syndrome. It is sometimes not possible to prove the presence of such a mutation, even when individuals have the appropriate combination of symptoms and the condition develops in a way characteristic of the syndrome. An investigation may then be carried out into the possible presence of mutations in the CDKL5 and FOXG1 genes.

At the time of diagnosis it is important that the family is offered genetic counselling. Carrier and prenatal diagnosis, as well as pre-implantation genetic diagnosis (PGD) in association with IVF (in vitro fertilization), are available to families where the exact mutation is known.

As it is possible to be a carrier of a mutation in gene MECP2 and have only mild symptoms or none at all, women who have a child with this mutation should be offered a DNA test.

Rett syndrome can be more difficult to diagnose in boys. Boys known to have a mosaic form of the mutation, where the mutation is present in only a proportion of cells, can have the same symptoms as girls. Boys with a further genetic mutation associated with the presence of one Y chromosome and two X chromosomes (Klinefelter syndrome) may also have the same symptoms as girls with Rett syndrome.

Treatment/interventions

There are currently no treatments or preventive measures which can cure the condition or stop its development. Instead, efforts are focused on treating and alleviating symptoms, preventing and attempting to compensate for loss of functions, as well as creating the most stimulating environment and the best quality of life possible.

The child and family require habilitation from an early stage in a programme based on the individual child's symptoms and abilites. Research shows that it is possible for those with Rett syndrome to develop with the help of special training and teaching. It is therefore important that individuals with Rett syndrome are offered appropriate support to help make use of their remaining abilities and to stimulate further development. Habilitation teams include professionals with expertise on disabilities and their effects on health, development and everyday life. Help is available within the medical, educational, psychological, social and technical fields. Habilitation may include assessments, treatment, assistance with choice of aids, information about disabilities and counselling.

Information is also given about support offered by public services as well as advice on the way accommodation and other environments can be adapted to the child’s needs. Parents, siblings and other relatives should be offered support. There should be close contact with the local authority, which can offer different kinds of help including personal assistance, a contact family or short-term accommodation, to make daily life easier.

Gastrointestinal and feeding problems

Feeding can take time as many have respiratory and swallowing problems. Speech/language pathologists (speech therapists) and occupational therapists can give advice and support on feeding techniques, how to choose appropriate cutlery and seating positions which facilitate swallowing. Substances which change the consistency of the food can be tried. Contact is required with a dietician who is familiar with the consequences of respiratory abnormalities and with determining nutritional energy content, and with providing advice on dietary supplements. Forceful breathers may need considerably more fluids and calories than other individuals.

Sometimes a direct connection between the abdominal wall and the stomach, a PEG (percutaneous endoscopic gastrostomy) is necessary to facilitate feeding. However, to stimulate the sense of taste, smaller portions should always be given by mouth if there is not a major risk of choking (aspiration).

Painful lesions can develop in the lower part of the oesophagus due to the reflux of acid from the stomach. It may require life-long medication. An operation may sometimes be required to ensure that the cardia (the part of the stomach attached to the oesophagus) can close effectively.

Constipation can be helped by preventive measures including drinking lots of fluids, eating fibre-rich food, providing a relaxed and calm environment, stomach massage and regular toileting. Laxative medication to treat constipation may also be necessary.

Preventing malpositioning

Abnormal muscle tone (excessively low, excessively tight, asymmetric) is found in different degrees in everyone with Rett syndrome. Changes in muscle tone happen successively over time. All children should be examined as soon as the diagnosis is made so that preventive measures can be taken and followed up. This examination should include the legs, feet, arms, spine, pelvis and hips. During growth spurts the child's condition can deteriorate rapidly.

Treatment is based on planned, regular, daily physical activity which is fun for the child. A seating position which offers stability and support is important in preventing deformities, as a good sitting position makes balancing the body easier. A good sitting position is important in both wheelchairs and chairs used for other activities. For individuals who cannot stand or walk themselves, daily practice in standing with the help of various aids is good for the skeleton and helps prevent joint malpositioning and contractures. It also helps lung and gastrointestinal function. The ability to stand can be retained if individuals use, for example, a standing frame. It should also be possible for them to change position and stretch to their full height. Weight-bearing and muscle-strengthening exercises both help prevent factures. A well-rounded diet including calcium and vitamins is important.

Exercises which increase mobility and strength can improve physical balance and symmetry as well as postponing or preventing malpositioning and contractures. These include water-based exercise, exercise to music, and riding. Treatment also includes massage for tense muscles. As people with Rett syndrome cannot usually talk or grip objects, the ability to move is especially important as it gives them a means of expressing their own wishes and needs.

A supportive orthopaedic brace can improve balance. Orthopaedic braces to treat scoliosis have also been tried but the treatment has proved very difficult for the children and has not achieved the desired result as surgical intervention has still been required. Movement, strength and general good physical fitness are all important before an operation. The surgeon needs to be familiar with and have special expertise in treating the syndrome.

Standing and walking with the help of well-fitting orthopaedic supports and appliances is the best way to prevent shortening of the tendons in the calves. Foot abnormalities should be examined by an orthopaedic surgeon in consultation with a paediatric neurologist with experience of Rett syndrome. Treatment can involve injections of the botulinum toxin into the muscles, or corrective operations to move or extend the tendons.

Development and communication

People with Rett syndrome must be able to develop their motor and communication skills according to their individual capacities. As they find it difficult to take the initiative and take purposeful actions (apraxia/dyspraxia) there is a long delay before they answer. For this reason, motivation should be actively stimulated. Most of those with the syndrome enjoy listening to music and stories, and carrying out manageable tasks.

The enjoyment and motivation associated with music are invaluable in the contexts of two-way communication and learning. Research has shown that specially selected music is very important for people with Rett syndrome, both for its ability to affect the autonomic nervous system in the context of communication, and as a tool for individuals to show what they can achieve. Music offers an opportunity for people with the syndrome to show others their cognitive strengths so it should be made available in as many contexts as possible.

An investigation will provide the basis for deciding which form of alternative and complementary communication (ACC) to use. People with the syndrome retain most control over their ocular function. Eye function usually remains good and serious changes to, or impairment of, vision are unusual. The ability to control eye movements and indicate direction can be used to communicate throughout life. Eye-controlled computer screens are being developed and can be used for learning and communication. Girls with Rett syndrome require the specialist teaching methodology found, among other places, in special schools.

Adults with Rett syndrome require continued individual habilitation measures and contact with general medical services, as well as with certain specialists including a neurologist and an orthopaedic surgeon. Support and care is required in daily life, for example in accommodation offering specialist services and daily activities. Personal assistance enables individuals with Rett syndrome to participate in activities and improves their quality of life.

Respiration, cardiovascular function and peripheral circulation

It is important to discover what type of breathing abnormality the child has, how it affects cardiovascular function and metabolism, and type of seizures. The type and extent of the breathing abnormalities determine their treatment. Certain types of respiratory abnormalities can be treated with medication, while others may require breathing aids.

Regular physical activity is important in Rett syndrome as it strengthens central autonomic control in the brain stem. Good levels of control affect, for example, the stability of blood pressure and pulse and also the ability to adjust to levels of stress in one's environment. They also affect concentration and hence, the ability to learn. Stress and lack of physical activity reduce control of, and so increase, autonomic abnormalities including significant changes in blood pressure, seizures, insomnia, gastrointestinal symptoms, panic attacks and difficulties in concentrating and learning.

The blood pressure of people with Rett syndrome is commonly rather low. They have normal orthostatic reactions but should be allowed some extra time when standing up to avoid the dizziness associated with a fall in blood pressure.

Morphine, morphine derivatives and benzodiazepines should not be prescribed for people who belong either to the category "feeble breathers" (who take superficial breaths) or "apneustic breathers" (those who take long pauses between breaths) as they can be over-sensitive to these medications.

As well as wearing warm footwear, feet can be kept warm by foot massages and heated socks, or other foot-warming devices. During sleep the feet become warm.

Epileptic and non-epileptic seizures

Epilepsy is treated with various medications to prevent the different types of seizures, but it can be difficult to stop attacks completely. Sometimes medication can be successively reduced, or stopped entirely, in adulthood. It can be difficult to distinguish between epileptic seizures and non-epileptic seizures which originate from the brain stem.

The origins of these seizures should therefore be investigated and identified in a combined neurophysiological examination of both the cerebrum and the brain stem simultaneously. At the same time, levels of blood gases in tissue and in the central autonomic system should be measured. Treatment will depend on the results of the measurements.

Dental care and jaw problems

Tooth brushing and dental treatment can be problematical for the individual, so supplementary preventive care is necessary. A paedodontist (a dentist specializing in children) should be consulted at an early stage to make a dental examination and plan treatment. When necessary, tooth-grinding should be followed up and a dental bite guard provided.

Jaw and neck muscles may be tense and painful and specialist massage can assist relaxation.

Insomnia, agitation and over-excitement

Melatonin treatment has been tried, with varying results. Sometimes breathing aids can be needed at night.

It is important to avoid stimuli which might cause agitation and over-excitement. Regular, daily activities which can promote calm and reduce agitation and excitement are useful. These include certain types of music and songs, massage, physical closeness and warm baths. Risperidone may sometimes be used in cases of severe anxiety. In order to ensure the safety of the person taking this medication, the type of breathing abnormality he or she has should be identified before treatment starts.

Practical advice

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National and regional resources in Sweden

The Swedish National Rett Center is a center of expertise offering clinical diagnostics and medical assessments including brain stem examinations (corticobulbar neurophysiology) and training. It is also a center for multi-disciplinary research and the spread of knowledge and information. The Rett Center, Frösö Strand, Box 601, SE-832 23 Frösön, Sweden.Tel: +46 63 15 48 10, fax: +46 63 15 45 00, email: rettcenter@jll.se, www.rettcenter.se. Contact Senior Physician Ingegerd Witt Engerström. Tel: +46 705 56 52 57, email: ingegerd.witt.engerstrom@ljj.se.

A multi-disciplinary team with expertise in neuropaediatrics and respiratory physiology is located at the Astrid Lindgren Children's Hospital and the Karolinska Institute. Contact Maud Eriksson, tel: +46 8 585 800 00.

Diagnoses of Rett syndrome can be made at The Queen Silvia Children's Hospital in Gothenburg, Sweden. Contact Senior Physician Barbro Westerberg, Children and Young Person's Habilitation. Tel: +46 31 343 40 00.

At Habilitation and Health, Stockholm County Council, there is a multi-disciplinary team with expertise in Rett syndrome, www.habilitering.nu/ovanligadiagnoser. Contact Kristina Gustafsson-Bonnier, tel: +46 8 690 35,023 33, email: kristina.gustafsson-bonnier@sll.se.

Expertise in Rett-related orofacial problems can be found at Mun-H-Center, Institute of Odontology, Gothenburg, Medicinaregatan 12 A, SE-413 90 Gothenburg, Sweden. Tel: +46 31 750 92 00, fax: +46 31 750 92 01, email: mun-h-center@vgregion.se, www.mun-h-center.se.

Resource personnel

Senior Physician Maud Eriksson and Dr Rickard Nergårdh, Astrid Lindgren Children's Hospital in Huddinge, SE-141 86 Stockholm, Sweden. Tel: +46 8 585 800 00. Also Senior Physician Margareta Albåge, Associate Professor Miriam Katz-Salamon and Dr Malin Rohdin, Astrid Lindgren Children's Hospital in Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 700 00.

Professor Christopher Gillberg, University of Gothenburg, Gillberg Centre, Kungsgatan 12, SE-411 19 Gothenburg, Sweden. Tel: +46 31 342 5970 70, email: christopher.gillberg@gnc.gu.se.

Senior Dental Surgeon Karin Högkil, Eastmaninstitutet, Dalagatan 11, SE-113 24 Stockholm, Sweden. Tel: +46 8 123 165 38.

Associate Professor Barbro Westerberg, The Queen Silvia Children's Hospital, SE-416 85 Gothenburg, Sweden. Tel: +46 31 343 40 00.

Senior Physician Ingegerd Witt Engerström and her associates at the Swedish National Rett Center, Frösö Strand, Box 601, SE-832 23 Frösön, Sweden. Tel: +46 63 15 48 10, email: ingegerd.witt.engerstrom@jll.se, tel: +46 705 56 52 57. For more information see www.rettcenter.se.

Courses, exchanges of experience, recreation

Family conferences and camps are organized by the association, Rett Syndrome in Sweden (RSIS). For further information contact RSIS.( Find address under, "Organizations for the disabled/patient associations etc.")

Ågrenska's families programme arranges stays for children and young people with disabilities and their families. Ågrenska is open to families from the whole of Sweden and focuses particularly on the needs of children and young people with rare diseases. A number of programmes every year is also provided for adults with rare diseases. Information is available from Ågrenska, Box 2058, SE-436 02 Hovås, Sweden. Tel: +46 31750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se, www.agrenska.se.

Organizations for the disabled/patient associations etc.

Rett Syndrome in Sweden (RSIS), email: info@rsis.se, www.rsis.se. Chair is Katarina Öryd, katarina.oryd@rsis.se.

Rare Diseases Sweden, Sturegatan 4A, Box 1386, SE-172 27 Sundbyberg, Sweden. Tel: +46 8 764 49 99, email: info@sallsyntadiagnoser.se, www.sallsyntadiagnoser.se. Rare Diseases Sweden is a national association representing people with rare diseases and varying disabilities.

There is an international association, International Rett Syndrome Foundation (IRSF), www.rettsyndrome.org, also a European association, Rett Syndrome Europe (RSE), www.rettsyndrome.eu.

Courses, exchanges of experience for personnel

Courses, workshops, conferences and seminars for multi-disciplinary teams or specialist groups within habilitation, healthcare and schools, are organized by the Rett Center. For further information contact RSIS. (Find address under, "National and regional resources in Sweden.")

Courses for personal assistants are organized by the association, Rett Syndrome in Sweden (RSIS), in collaboration with the Rett Center. For further information contact RSIS or the Rett Center. (Find address under, "Organizations for the disabled/patient associations etc.")

Research and development

Clinical research in several areas is ongoing at the Rett Center. Research areas include the functions of the brain stem, central autonomic control and respiration, and central autonomic control and gross motor skills. Other areas include the role of music in the brain stem’s regulatory effect on the autonomic nerve system, peripheral circulation and temperature, and both activity and communication in Rett syndrome. Long term clinical monitoring of people with the condition has been carried out for the last 25 years.

Research in the area of respiratory physiology is under way at the Astrid Lindgren Children's Hospital in Solna/Huddinge and the Karolinska Institute, Sweden. For contacts, see under "Resource personnel."

Information material

Short summaries of all the database texts are available as leaflets, in Swedish only. They can be printed out or ordered by selecting the Swedish version, and then clicking on the leaflet icon which will appear under, "Mer hos oss" in the column on the right-hand side.

Julu PO, Witt Engerström I, Hansen S et al. Kardiorespiratoriska störningar vid Rett syndrom – en utmaning för Hälso- och sjukvården: Frösödeklarationen (in Swedish only). This can be downloaded at www.rettcenter.se and can also be ordered from the Rett Center. Find address under "National and regional resources in Sweden."

Information folders (in Swedish and English) on Rett syndrome, brain stem examinations, music therapy, the Rett Center and Accomodation at the Rett Center. This may be downloaded at: www.rettcenter.se. A pocket-size information folder (in Swedish only) can be ordered from RSIS, email info@rsis.nu.

Ågrenska has published information on Rett syndrome, nr 448 (2013). In Swedish only. These newsletters are edited summaries of lectures delivered at family and adult stays at Ågrenska. They may be ordered from Ågrenska, Box 2058, SE-436 02 Hovås, Sweden. Tel: +46 31 750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se. They are also available at www.agrenska.se.

Rett syndrome. Information folder (in Norwegian only) from Senter for sjeldne funksjonshemninger, Frambu and the Norwegian Association for Rett Syndrome (2010). Order from, Senter for sjeldne funksjonshemninger, Informasjonsseksjonen, NO-1404 Siggerud, Norway.Tel: +47 64 85 60 00, email: info@frambu.no.

Films

Musorik classes (music and motor skills). Run by Märith Bergström-Isacsson, music therapist and Gunilla Larsson, physiotherapist, Rett Center, Sweden 2008. Can be ordered from the Rett Center. Find address under "National and regional resources in Sweden." The film is also available in English.

(Jag talar med ögonen.) I speak with my eyes - Retts syndrome. The film can be ordered from RSIS, email: info@rsis.nu.

The Musement. A rhythmic movement class for children with Rett syndrome or any children who like to move to music. By Märith Bergström-Isacsson, music therapist and Gunilla Larsson, physiotherapist, Rett Center, Frösön, Sweden 2008. Can be ordered from the Rett Center. Find address under "National and regional resources in Sweden."

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Bergstrom-Isacsson M, Julu POO, Witt-Engerstrom I. Autonomic responses to music and vibroacoustic therapy in Rett syndrome: A controlled within-subject study. Nordic J Music Therapy 2007; 16.

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Hagberg B, Aicardi J, Dias K, Ramos O. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand in girls: Rett syndrome: report of 35 cases. Annals of Neurology. 1983, 14: 471-479.

Halbach N S J, Smeets E E J, van den Braak N, van Roozendaal K E P, Blok R M J, Schrander-Stumpel C T R M et al. Genotype –Phenotype Relationships as Prognosticators in Rett Syndrome Should be Handled With Care in Clinical Practice. Am J Med Genet 2011; 1-11.

Halbach NS, Smeets EE, Bierau J, Keularts I, Plasqui G, Julu PO, et al. Altered Carbon Dioxide Metabolism and Creatine Abnormalities in Rett syndrome. JIMD Rep . 2012: 3: 117-24.

Julu PO, Kerr AM, Apartopoulus F, Al-Rawas S, Witt Engerström I, Engerström L. Characterisation of breathing and associated central autonomic dysfunction in the Rett disorder. Arch Dis Child 2001; 85: 29-37.

Julu PO, Witt Engerström I. Assessment of the maturity related brainstem functions reveals the heterogeneous phenotypes and facilitates clinical management of Rett syndrome. Brain Dev 2005; 27: 43-53.

Julu PO, Witt Engerström I, Hansen S, Apartopoulos F, Engerström B, Pini G et al. Cardiorespiratory challenges in Rett’s syndrome. Lancet 2008; 371: 1981-1983.

Julu PO O, Witt Engerström I, Hansen S, Apartopoulos F, Enger¬ström B. Treating hypoxia in a feeble breather with Rett syndrome. Brain Dev. 2013; 35: 270-3.

Kerr AM, Webb P, Prescott RJ, Milne Y. Results of surgery for scoliosis in Rett syndrome. J Child Neurol 2003; 18: 703-708.

Larsson G, Witt Engerström I. Gross motor ability in Rett syndrome – the power of expectation, motivation and planning. Brain Dev 2001; 23: 77-81.

Larsson G, Lindström B, Witt Engerström I. Rett syndrome from a family perspective; The Swedish Rett Center survey. Brain Dev 2005; 27: 14-19.

Larsson G, Julu P O O, Witt Engerström I, Sandlund M, Lindström B. Normal reactions to orthostatic stress in Rett syndrome. Research in Developmental Disabilities 2013; 34:1897-1905.

Lavås J, Slotte A, Jochym-Nygren M, van Doorn J, Witt Engerström I. Communication and eating proficiency in 125 females with Rett syndrome -The Swedish Rett Center Survey. Disabil Rehabil 2006; 28: 1267-1279.

Marschik P, Kaufman W, Sigafos J, Wolin T, Zhang D, Bartl-Pokorny K, et al. Changing the perspective on early development of Rett syndrome. Research in Developmental Disabilities 2013; 34: 1236-1239.

Neul JL, Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi-Buisson N et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010; 68: 944-50.

Nomura Y. Early behavior characteristics and sleep disturbances in Rett syndrome. Brain Dev 2005; 27: 35-42.

Nomura Y, Kerr A, Witt Engerström I (eds). Rett syndrome; early behavior and possibilities for intervention. Brain Dev Supplement 1, 2005.

Percy, AK. Neuroscience. Path to treat Rett syndrome.Science 2013; 18: 318-20.

Qvarfordt I, Witt Engerström I, Eliasson A-C. Guided eating or passive feeding – Three girls with Rett syndrome. Scand J Occupational Therapy 2008; 7: 1-7.

Rett A: Über ein eigenartiges hirnatrophisches Syndrom bei Hyperammonämie im Kindesaler. Wiener medizinische Wochenschrift, 1966, 116: 723-726.

Roende G, Ravn K, Fuglsang K, Andersen H, Vestergaard A, Bröndum-Nielsen K, et al. Patients with Rett syndrome sustain low-energy fractures. Pediatric Research 2011.

Rohdin M, Fernell E, Eriksson M, Albåge M, Lagercrantz H, Katz-Salamon M. Disturbances in cardiorespiratory function during day and night in Rett syndrome. Pediatr Neurol 2007; 37: 338-344.

Smeets E.E.J, Julu P O O, van Wardenburg D, Engerström IW, Hansen S, Apartopoulos F, et al. Management of a severe forceful breather with Rett Syndrome using carbogen. Brain Dev 2006; 28: 625-632.

Books

Halbach N. Clinical management of Rett syndrome. Medical dissertation Maastricht University June, 2013. Can be downloaded at: http://digitalarchive.maastrichtuniversity.nl/fedora/get/guid:ce1867e0-f041-4bbc-b5a5-c46b32cc71b2/ASSET1

Larsson Gunilla. Rett syndrome, motor development, mobility and orthostatic reactions. Medical dissertation Umeå University and the Swedish Rett Center May, 2013. Can be downloaded at: http://www.diva-portal.org/smash/record.jsf;jsessionid=27311f34ba2de8049e29c31012f3?parentRecord=diva2:616694&pid=diva2:617400.

Bergström-Isacsson Märith. Music and vibroacustic stimulation of persons with Rett syndrome – A neurophysiological study. Dissertation Ph, Humanistic faculty, Aalborg University and the Swedish Rett Center 2011.

The Rett syndrome handbook with CD. Can be ordered from the International Rett Syndrome Foundation (IRSF), www.rettsyndrome.org.

Kerr A, Witt Engerström I. Rett disorder and the developing brain.
Oxford University Press 2005. Oxford University Press 2005.

Lindberg B. Understanding Rett syndrome – A practical guide for parents, teachers and therapists. Second revised edition, Hogrefe 2006.

Lotan M, Merrick J. Rett syndrome – Therapeutic interventions. Nova Science publishers 2011.

Smeets, Eric EJ. Rett Syndrome 1954-2004. Ph.D thesis Maastricht University, 2005. Can be downloaded at: http://arno.unimaas.nl/show.cgi?fid=6362.

Witt Engerström Ingegerd. Rett syndrome in Sweden. Neurodevelopment – Disability – Pathophysiology. Almqvist & Wiksell International,1990.

Database references

OMIM (Online Mendelian Inheritance in Man)
www.ncbi.nlm.nih.gov/omim 
Search: Rett syndrome

GeneReviews (University of Washington)
www.genetests.org (select "GeneReviews", then "Titles")
Search: Rett syndrome

Orphanet, www.orpha.net 
Search: Rett syndrome

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical experts who wrote the draft of this information material are Professor Emeritus Bengt Hagberg, The Queen Silvia Children's Hospital in Gothenburg, and Senior Physician Ingegerd Witt Engerström, Swedish National Rett Center, Frösö Strand.

The material has been revised by Senior Physician Ingegerd Witt Engerström, Rett Center, Frösö Strand, Sweden.

The relevant organizations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Date of publication: 2014-10-08
Version: 4.0
Publication date of the Swedish version: 2014-03-25

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 422, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.

 

About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.